Rationale: Retinopathy of Prematurity (ROP) remains a serious public health problem causing significant visual sequelae. It is estimated that 2,060 premature survivors in 1991 in the United States would be adversely affected by ROP, despite the now recognized use of Cryotherapy (estimates prior to Cryotherapy would have been 4,480). Case control studies in premature infants, anecdotal reports of successful treatment of moderately severe ROP with oxygen, and studies conducted in an animal model which induced chronic (weeks-long) hypoxia by breathing 13% inspired oxygen (mean PaO2=38) during the model's healing process, suggest that hypoxia may be a critical factor associated with and perhaps influencing cases that progress rather than regress. This hypothesis is supported by the association of proliferative retinopathies with retinal hypoxia in other disorders such as diabetic or sickle cell retinopathy. These data justify testing of the hypothesis that Supplemental Therapeutic Oxygen for Prethreshold ROP (STOP-ROP) will reduce, by at least one third, the number of infants with one or both eyes progressing to Threshold ROP. Design: This is a randomized, blinded, multicenter study utilizing 24 centers. 880 infants who develop Prethreshold ROP (as defined by STOP-ROP, modified from the CRYO-ROP study) will receive continuous pulse oximetry saturation monitoring and be randomly assigned to oxygen administration at one of two specified oxygen levels, "conventional" with pulse oximetry of 89-94% saturation vs "supplemental" with pulse oximetry of 96-99% saturation. Their ROP status will be measured and recorded prospectively, and the primary outcome variable will be the proportion of infants who progress to Threshold ROP in at least one eye by 3 months after their expected date of full term delivery. Secondary outcome measures include other ophthalmic (e.g. retinal detachment, macular ectopia) and neonatal outcomes (e.g. growth, pulmonary status, length and cost of hospital stay). The projected sample size is compatible with a 2-3 year enrollment.